The long-term objectives of this study are to determine specific and detailed events in vivo that occur within articular cartilage, during turnover, degradation and regeneration. To achieve these objectives, this project will determine: 10 the change in concentrations of specific matrix components in articular cartilage of knee joints of greyhounds subjected to normal joint use, joint disuse, joint disuse followed by specified periods of recovery, and joint disuse followed by specific periods of strenuous exercise; 2) the concentration of these matrix components in synovial fluids of greyhound knee joints; 3) the concentrations of selected specific matrix components in sequential blood samples of the dogs during periods of disuse, recovery and strenuous exercise; 40 the concentrations of these matrix components in articular cartilage of knee joints from the Pond-Nuki dog model of osteoarthritis (OA) at different stages of disease progression; and 5) the concentration of matrix components in synovial fluids of knee joints and in sequential blood samples of the OA dogs. All tissues will be made available by Drs. V. C. Mow, J.C. Pita and D.S. Howell, from work currently pursued under NIH grant #AR38733. The analyses will make quantitative determinations of specific cartilage matrix components. These will include proteoglycan components (large aggregating type and small proteoglycan), specific collagen-related components and other selected matrix components (link protein, 559kDa protein and 148kDa protein). The selection of components to be studied is intended to provide a detailed profile of the content of major quantitative and functional matrix components in the cartilage, synovial fluid and serum of the dogs in disuse and OA. This project combines the use of advanced immunochemical and biochemical analyses, together with a set of unique research tissues. It is a detailed but selective approach designed to assess our hypotheses of cartilage changes, and provide an advanced understanding of the different metabolic events that occur within articular cartilage.